Alternative titles; symbols
HGNC Approved Gene Symbol: DDX5
Cytogenetic location: 17q23.3 Genomic coordinates (GRCh38): 17:64,498,254-64,506,866 (from NCBI)
DEAD box proteins are putative RNA helicases that have a characteristic Asp-Glu-Ala-Asp (DEAD) box as 1 of 8 highly conserved sequence motifs. The p68 protein is a proliferation-associated nuclear antigen first identified through its highly specific cross-reaction with the simian virus 40 tumor antigen (Iggo et al., 1989). Subsequently, homology to eukaryotic translation initiation factor was found, and amino acid sequence blocks characteristic of a large superfamily of proteins with putative helicase activity were demonstrated. Hloch et al. (1990) reported the complete cDNA sequence of the p68 gene.
Using a library of endoribonuclease-prepared short interfering RNAs (esiRNAs), Kittler et al. (2004) identified 37 genes required for cell division, one of which was DDX5. These 37 genes included several splicing factors for which knockdown generates mitotic spindle defects. In addition, a putative nuclear-export terminator was found to speed up cell proliferation and mitotic progression after knockdown.
By immunoprecipitation analysis, Caretti et al. (2006) found that p68, p72 (DDX17; 608469), and the noncoding RNA SRA (SRA1; 603819) associated with MYOD (MYOD1; 159970) in MYOD-transfected HeLa cells. In vitro and in vivo experiments identified p68, p72, and SRA as coactivators of MYOD, and their knockdown in C2C12 mouse myoblast cells prevented proper muscle gene expression and cell differentiation. Short hairpin RNA-mediated knockdown of p68 and p72 in C2C12 cells led to reduced expression of a broad spectrum of genes, including genes involved in muscle structure, metabolism, neurophysiologic processes, transcription and chromatin regulation, and signal transduction. Further experiments showed that p68 and p72 played critical roles in promoting the assembly of proteins required for formation of the transcription initiation complex and chromatin remodeling.
Yang et al. (2006) found that phosphorylation of p68 at tyr593 was necessary for PDGF (see 190040)-stimulated epithelial-mesenchymal transition (EMT) in HT-1 human epithelial colon cancer cells. PDGF treatment activated ABL (189980), which subsequently phosphorylated p68 at tyr593 in the nucleus. Phosphorylated p68 promoted beta-catenin (CTNNB1; 116806) nuclear translocation via a WNT (see 164820)-independent pathway. Phosphorylated p68 interacted with nuclear beta-catenin, which subsequently stimulated EMT.
Davis et al. (2008) demonstrated that induction of a contractile phenotype in human vascular smooth muscle cells by TGF-beta (190180) and bone morphogenetic proteins (BMPs; see 112264) is mediated by miR21 (611020). miR21 downregulates PDCD4 (608610), which in turn acts as a negative regulator of smooth muscle contractile genes. TGF-beta and BMP signaling promoted a rapid increase in expression of mature miR21 through a posttranscriptional step, promoting the processing of primary transcripts of miR21 (pri-miR21) into precursor miR21 (pre-miR21) by the Drosha complex (see 608828). TGF-beta and BMP-specific SMAD signal transducers SMAD1 (601595), SMAD2 (601366), SMAD3 (603109), and SMAD5 (603110) are recruited to pri-miR21 in a complex with the RNA helicase p68, a component of the Drosha microprocessor complex. The shared cofactor SMAD4 (600993) is not required for this process. Thus, Davis et al. (2008) concluded that regulation of microRNA biogenesis by ligand-specific SMAD proteins is critical for control of the vascular smooth muscle cell phenotype and potentially for SMAD4-independent responses mediated by the TGF-beta and BMP signaling pathways.
Iggo et al. (1989) found that they could not map the p68 gene through use of Southern blot analysis and human p68 cDNA probes. A complex pattern was seen with both human and rodent DNA. The human p68 gene could not be identified, presumably because of conservation of the p68 gene in man and mouse. From surmises of the location of splice sites in human p68 on the basis of examination of the gene structure of conserved regions in homologous genes, Iggo et al. (1989) chose 2 sets of primers that they predicted would lie on either side of the splice sites. Using these probes for the study of hybrid cell lines and cell lines developed using chromosome-mediated gene transfer, they showed that the gene was located in the area 17q23-q25.
Brody et al. (1995) confirmed that this gene is located on chromosome 17 in the region of the BRCA1 gene at 17q21.
The article by Huang et al. (2015) identifying Ddx5 as an Ror-gamma-t (see 602943)-interacting protein in mouse T-helper-17 (Th17) cells (see IL17A, 603149) and concluding that gly270 in the long noncoding RNA Rmrp (157660) was critical for Ddx5-Ror-gamma-t complex assembly and for recruitment of Rmrp to Ror-gamma-t loci to coordinate the Th17 effector program was retracted because key aspects of the original results could not be replicated.
Brody, L. C., Abel, K. J., Castilla, L. H., Couch, F. J., McKinley, D. R., Yin, G.-Y., Ho, P. P., Merajver, S., Chandrasekharappa, S. C., Xu, J., Cole, J. L., Struewing, J. P., Valdes, J. M., Collins, F. S., Weber, B. L. Construction of a transcription map surrounding the BRCA1 locus of human chromosome 17. Genomics 25: 238-247, 1995. [PubMed: 7774924] [Full Text: https://doi.org/10.1016/0888-7543(95)80131-5]
Caretti, G., Schiltz, R. L., Dilworth, F. J., Di Padova, M., Zhao, P., Ogryzko, V., Fuller-Pace, F. V., Hoffman, E. P., Tapscott, S. J., Sartorelli, V. The RNA helicases p68/p72 and the noncoding RNA SRA are coregulators of MyoD and skeletal muscle differentiation. Dev. Cell 11: 547-560, 2006. [PubMed: 17011493] [Full Text: https://doi.org/10.1016/j.devcel.2006.08.003]
Davis, B. N., Hilyard, A. C., Lagna, G., Hata, A. SMAD proteins control DROSHA-mediated microRNA maturation. Nature 454: 56-61, 2008. [PubMed: 18548003] [Full Text: https://doi.org/10.1038/nature07086]
Hloch, P., Schiedner, G., Stahl, H. Complete cDNA sequence of the human p68 protein. Nucleic Acids Res. 18: 3045, 1990. [PubMed: 2349099] [Full Text: https://doi.org/10.1093/nar/18.10.3045]
Huang, W., Thomas, B., Flynn, R. A., Gavzy, S. J., Wu, L., Kim, S. V., Hall, J. A., Miraldi, E. R., Ng, C. P., Rigo, F., Meadows, S., Montoya, N. R., and 9 others. DDX5 and its associated lncRNA Rmrp modulate T(H)17 cell effector functions. Nature 528: 517-522, 2015. Note: Erratum: Nature 533: 130 only, 2016. Retraction: Nature 562: 150 only, 2018. [PubMed: 26675721] [Full Text: https://doi.org/10.1038/nature16193]
Iggo, R., Gough, A., Xu, W., Lane, D. P., Spurr, N. K. Chromosome mapping of the human gene encoding the 68-kDa nuclear antigen (p68) by using the polymerase chain reaction. Proc. Nat. Acad. Sci. 86: 6211-6214, 1989. [PubMed: 2762324] [Full Text: https://doi.org/10.1073/pnas.86.16.6211]
Kittler, R., Putz, G., Pelletier, L., Poser, I., Heninger, A.-K., Drechsel, D., Fischer, S., Konstantinova, I., Habermann, B., Grabner, H., Yaspo, M.-L., Himmelbauer, H., Korn, B., Neugebauer, K., Pisabarro, M. T., Buchholz, F. An endoribonuclease-prepared siRNA screen in human cells identifies genes essential for cell division. Nature 432: 1036-1040, 2004. [PubMed: 15616564] [Full Text: https://doi.org/10.1038/nature03159]
Yang, L., Lin, C., Liu, Z.-R. P68 RNA helicase mediates PDGF-induced epithelial mesenchymal transition by displacing Axin from beta-catenin. Cell 127: 139-155, 2006. [PubMed: 17018282] [Full Text: https://doi.org/10.1016/j.cell.2006.08.036]